• Fig. 33.23 Examples of the interactions of endothelial cells with smooth muscle and mesangial cells. ACE, angiotensin-converting enzyme; AI, angiotensin I; AII, angiotensin II. (Modified from Navar LG et al. Physiol Rev 1996;76:425.) Smooth muscle cell or mesangial cellVasodilation PGI2 PGE2 Nitric oxide Stretch Histamine Acetylcholine Bradykinin ATP A I A II Endothelin A C E Endothelial cell Vasoconstriction
Finally, as illustrated in
Fig. 33.23 , endothelial cells play an important role in regulating the resistance of the renal afferent and efferent arterioles by producing a number of paracrine hormones, including NO, prostacyclin (PGI2), endothelin, and angiotensin II. These hormones regulate contraction or relaxation of smooth muscle cells in afferent and efferent arterioles and mesangial cells. Shear stress, acetylcholine, histamine, bradykinin, and ATP stimulate production of NO, which increases GFR and RBF. Angiotensin-converting enzyme (ACE), located on the surface of endothelial cells lining the afferent arteriole and glomerular capillaries, converts angiotensin I to angiotensin II, which decreases GFR and RBF. Angiotensin II is also produced locally by granular cells in the afferent arteriole and by proximal tubular cells. PGI2 and PGE2 release by endothelial cells is stimulated by both sympathetic nerve activity and angiotensin II, resulting in increased GFR and RBF. Finally, endothelin release from endothelial cells decreases both RBF and GFR.
ACE proteolytically inactivates the vasodilatory hormone bradykinin and converts angiotensin I, an inactive hormone, to angiotensin II, an active vasoconstrictive hormone. Thus ACE increases angiotensin II levels and decreases bradykinin levels. ACE inhibitors (e.g., lisinopril, enalapril, and captopril) are used clinically to reduce systemic blood pressure in patients with hypertension by decreasing angiotensin II levels and elevating bradykinin levels. Both effects lower systemic vascular resistance, reduce blood pressure, and decrease renal vascular resistance, thereby increasing GFR and RBF. Angiotensin II receptor antagonists (e.g., losartan) are also used to treat hypertension. As their name suggests, they block the binding of angiotensin II to the angiotensin II receptor (AT1). These antagonists block the vasoconstrictor effects of angiotensin II on the afferent arteriole; thus they increase RBF and GFR. In contrast to ACE inhibitors, angiotensin II receptor antagonists do not inhibit kinin metabolism (e.g., bradykinin).
1.
The first step in urine formation is passive movement of a plasma ultrafiltrate from the glomerular capillaries into Bowman’s space. The term ultrafiltration refers to passive movement of a plasma-like fluid that has a very low concentration of proteins from the glomerular capillaries into Bowman’s space. The endothelial cells of glomerular capillaries are covered by a basement membrane that is surrounded by podocytes. The capillary endothelium, basement membrane, and foot processes of podocytes form the so-called filtration barrier.
2.
The juxtaglomerular apparatus is one component of an important feedback mechanism (i.e., tubuloglomerular feedback) that regulates RBF and GFR. The structures that make up the juxtaglomerular apparatus include the macula densa, extraglomerular mesangial cells, and reninand angiotensin II–producing granular cells.
3.
Clinically, GFR is frequently estimated using measures of plasma [creatinine] or CrCl.